Allogeneic ABCB5-positive Limbal Stem Cells for Treatment of LSCD

NCT03549299 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: LSC2-II-01
• Study Type: interventional
• Target: 16
• Locations: 2 countries
• Sites: 5

Brief Summary

The aim of this clinical trial is to investigate the efficacy (by monitoring neovascularization and epithelial defects) of up to four doses of the investigational medicinal product (IMP) LSC2 topically administered on the target eye of patients with LSCD. Further, safety of the IMP during and after application will be investigated (by monitoring adverse events \[AEs\]).

Conditions

Limbal Stem Cell Deficiency

Keywords

limbal stem cell deficiency; ABCB5; Limbal stem cells; LSCs; LSC; allogeneic; tissue engineered product; phase I/IIa

Outcome Measures

Primary Outcomes (2)

• Response rate at 12 months after IMP application

  Response rate at 12 months after IMP application, where response is defined as: * no or mild corneal neovascularization (no vessel penetration or vessel penetration up to 1 quadrant, without central cornea) AND * no or mild epithelial defects (no corneal erosion or ulcer are present (corneal wounds are closed) or minimal superficial staining)

  Month 12

• Assessment of adverse event (AE) occurrence

  All AEs occurring during the clinical trial will be registered, documented and evaluated.

  Up to 24 months.

Secondary Outcomes (13)

• Response rate at 3 months after IMP application

  Month 3

• Neovascularization

  Baseline, week 1, 2, 3, 4, 5, 6, 7, 12, month 6 and 12

• Epithelial defects

  Baseline, week 2, 4, 6, month 3, 6 and 12

• Ocular symptoms of pain, photophobia, burning

  Baseline, week 2, 4, 6, 12, month 6 and 12

• Ocular inflammation

  Baseline, week 2, 4, 6, 12, month 6 and 12

Study Arms (4)

LSC2; 7.5 x 10^4 cells

EXPERIMENTAL

Single dose of LSC2, 7.5 x 10\^4 cells per patient

Biological: LSC2

LSC2; 3.0 x 10^5 cells

EXPERIMENTAL

Single dose of LSC2, 3.0 x 10\^5 cells per patient

Biological: LSC2

LSC2; 8.0 x 10^5 cells

EXPERIMENTAL

Single dose of LSC2, 8.0 x 10\^5 cells per patient

Biological: LSC2

LSC2; 1.2 x 10^6 cells

EXPERIMENTAL

Single dose of LSC2, 1.2 x 10\^6 cells per patient

Biological: LSC2

Interventions

LSC2 BIOLOGICAL

Topical application of IMP on target eye

Also known as: Suspension of ABCB5-positive limbal stem cells in pre-filled syringe

LSC2; 1.2 x 10^6 cells; LSC2; 3.0 x 10^5 cells; LSC2; 7.5 x 10^4 cells; LSC2; 8.0 x 10^5 cells

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged 18 to 85 years
• Neovascularization: Vessel penetration of at least 2 quadrants, with central cornea involved
• Patients understand the nature of the procedure and are providing written informed consent prior to any clinical trial procedure
• Women of childbearing potential must have a negative blood pregnancy test at Visit 1
• Women of childbearing potential must be willing to use highly effective contraceptive methods during the course of the clinical trial

You may not qualify if:

• Compromised eyelid mobility and/or symblepharon; patient can be re-screened after appropriate treatment
• Presence of eyelid malposition; patient can be re-screened after appropriate treatment
• Active local ocular or systemic infection and/or inflammation. Patient can be re-screened after infection and/or inflammation is resolved.
• Tumor diseases or history of tumor disease
• Corneal erosion or ulcer is bigger than 4 mm2; corresponding to less than 95% of continuous corneal epithelium. Patient can be re-screened after erosion or ulcer is resolved (≤ 4 mm2).
• Positive for human immunodeficiency virus (HIV) 1 and/or 2 (diagnosed by serologic testing)
• Clinically significant or unstable concurrent disease or other clinical contraindications to stem cell transplantation
• History of glaucoma
• Contraindications to trial related procedures/substances including
• The surgical procedure (e.g. removing of the conjunctival pannus)
• Contact lens complications due to contact lens use in the proposed trial (based on the Efron Grading scale for standard clinical reference for contact lens complications)
• Tear secretion deficiency determined by Schirmer's test
• Allergy, sensitivity or intolerance to components/excipients of the IMP/ per protocol pre-planned concomitant medications
• Conjunctival scarring with fornix shortening
• General anesthesia (in case general anesthesia is required) or local anesthesia

Sponsors & Collaborators

• RHEACELL GmbH & Co. KG: lead
• FGK Clinical Research GmbH: collaborator
• Ticeba GmbH: collaborator
• Granzer Regulatory Consulting & Services: collaborator

Study Sites (5)

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, 02114, United States

Location

Universitäts-Klinikum Köln, Augenklinik

Cologne, 50937, Germany

Location

Universitäts-Klinikum Heidelberg, Kopfklinik

Heidelberg, 69120, Germany

Location

Universitäts-Klinikum Jena, Augenklinik

Jena, 07747, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Augenklinik und Poliklinik

Mainz, 55131, Germany

Location

MeSH Terms

Conditions

Limbal Stem Cell Deficiency

Condition Hierarchy (Ancestors)

Corneal Diseases; Eye Diseases

Study Officials

• Gerd U. Auffarth, Prof.Dr.med.

  Universitäts-Klinikum Heidelberg, Kopfklinik, Heidelberg, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Patients will be treated in up to four ascending dose groups. After the first treated patient of the first dose group (Group A) was followed for 2 weeks, a safety and tolerability assessment of the applied IMP dose will be conducted by an internal committee. The same approach applies to the second subject. Dose escalation and recruitment of additional patients into the second dose group (Group B) will depend on the safety and tolerability of the IMP in Group A. A safety and tolerability assessment will be conducted after the last treated patient of the first dose group (Group A) was followed for 12 weeks. The same approach applies to Group C and D.

Study Record Dates

• First Submitted: May 14, 2018
• First Posted: June 8, 2018
• Study Start: July 4, 2019
• Primary Completion: September 1, 2023
• Study Completion: September 1, 2023
• Last Updated: October 7, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (4); US (1)